Urinary antihypertensive drug metabolite screening using molecular networking coupled to high-resolution mass spectrometry fragmentation

Introduction Mass spectrometry is the current technique of choice in studying drug metabolism. High-resolution mass spectrometry in combination with MS/MS gas-phase experiments has the potential to contribute to rapid advances in this field. However, the data emerging from such fragmentation spectral files pose challenges to downstream analysis, given their complexity and size. Objectives This study aims to detect and visualize antihypertensive drug metabolites in untargeted metabolomics experiments based on the spectral similarity of their fragmentation spectra. Furthermore, spectral clusters of endogenous metabolites were also examined. Methods Here we apply a molecular networking approach to seek drugs and their metabolites, in fragmentation spectra from urine derived from a cohort of 26 patients on antihypertensive therapy. The mass spectrometry data was collected on a Thermo Q-Exactive coupled to pHILIC chromatography using data dependent analysis (DDA) MS/MS gas-phase experiments. Results In total, 165 separate drug metabolites were found and structurally annotated (17 by spectral matching and 122 by classification based on a clustered fragmentation pattern). The clusters could be traced to 13 drugs including the known antihypertensives verapamil, losartan and amlodipine. The molecular networking approach also generated clusters of endogenous metabolites, including carnitine derivatives, and conjugates containing glutamine, glutamate and trigonelline. Conclusions The approach offers unprecedented capability in the untargeted identification of drugs and their metabolites at the population level and has great potential to contribute to understanding stratified responses to drugs where differences in drug metabolism may determine treatment outcome

Diversity Issues in Pediatric Behavioral Health Care

Youth from racial/ethnic, sexual, and gender minority groups have significant disparities in health and mental health outcomes. While the literature suggests that evidence-based cognitive behavioral therapies benefit youth and families with minority or marginalized status, less research has focused specifically on these populations in pediatric behavioral health care. Existing evidence pointing to the potential positive impact of pediatric psychologists working with marginalized communities including racial/ethnic minority and LGBTQ youth will be reviewed, along with a brief discussion of the relevance of culturally adapted or tailored interventions in pediatric behavioral health care. Important considerations for practitioners working with minority or marginalized youth and families will be discussed, including issues of mistrust, stigma, and accessibility of services.https://nsuworks.nova.edu/cps_facbooks/1668/thumbnail.jp